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Federici grew up in Italy, and came to the US in 1967 to study for a PhD in philosophy at the University at Buffalo.[4] She taught at the University of Port Harcourt in Nigeria, and was Associate Professor and later Professor of Political Philosophy and International Studies at New College of Hofstra University.

She was co-founder of the International Feminist Collective, an organizer with the Wages for housework campaign, and was involved with the Midnight Notes Collective. She co-founded the Committee for Academic Freedom in Africa (CAFA). In 1995, she co-founded the Radical Philosophy Association (RPA) anti-death penalty project.

Federici connects this expropriation to women's unpaid labour, both connected to reproduction and otherwise, which she frames as a historical precondition to the rise of a capitalist economy predicated upon wage labor. Related to this, she outlines the historical struggle for the commons and the struggle for communalism. Instead of seeing capitalism as a liberatory defeat of feudalism, Federici interprets the ascent of capitalism as a reactionary move to subvert the rising tide of communalism and to retain the basic social contract.

She situates the institutionalization of rape and prostitution, as well as the heretic and witch-hunt trials, burnings, and torture at the center of a methodical subjugation of women and appropriation of their labor. This is tied into colonial expropriation and provides a framework for understanding the work of the International Monetary Fund, World Bank, and other proxy institutions as engaging in a renewed cycle of primitive accumulation, by which everything held in common—from water, to seeds, to our genetic code—becomes privatized in what amounts to a new round of enclosures.